JOURNAL OF NUCLEAR MEDICINE 5:807-810, 1964 PRELIMINARY NOTE Radioisotope Renogram in Kidney Transplants1'2 Merle K. Loken, Ph.D., M.D., Edward V. Staab, M.D., Robert L. Vernier, M.D. and William D. Kelly, M.D. Minneapolis Presently the radioactive renogram is being used to follow the clinical course of patients who have received a renal transplant. Collins et al ( 1 ) have recently reported their experience in a similar group. To date, Iodine-131 Hip puran ( Ortho-iodo-hippurate ) 1 has been used exclusively in these studies, a! though consideration is now being given to the use of Mercury-197-Chloromero drin and Iodine-125-Hippuran. Serial renograms have been performed on 15 patients, who have received a kidney from a close relative or a human cadaver. Varying doses of steroids and other immunosuppressive agents are being used to prevent a rejection reaction. The patient's clinical status and conventional kidney function tests are used together with the renogram to adjust the dosage of drugs used and to indicate the possible need for other treatment. A dual rate meter system with 2-inch diameter sodium-iodide crystals is being used. Collimation of the crystals provides an 8-inch distance from the crys tal face to skin to minimize differences due to depth of the kidney below the skin surface. These kidneys are transplanted into the anterior iliac fossae so that reno grams are performed with the patients supine. One probe is placed directly over the kidney. In most cases, the second probe serves as a control and is placed over the abdominal vasculature on the opposite side. The positioning of probes in smaller patients is quite critical because of the close proximity of the kidney trans plant to the bladder. The exact position of the kidney is known from surgery so that no localizing dose for the probe placement is necessary. A dose of 20 @scof Iodine-131 Hippuran is administered intravenously as a bolus. Activity is dis played on a strip chart recorder with overlapping pens. The recorder is run at a speed of 3 inches per minute during the first minute and 12 inches per hour for the remainder of the examination. Thirty minute records are usually obtained. Renograms are obtained when possible on prospective donors. Following transplantation, an initial renogram is obtained while the recipient is in the post ‘Fromthe Departments of Radiology, Pediatrics and Surgery, University of Minnesota Hospitals. ‘Supported in part by funds from the United States Public Health Service Grant No. CA 03332-07 and the Graduate School, University of Minnesota. ‘CourtesyE. R. Squibb & Company. 807 808 LOKEN, STAAB, VERNIER AND KELLY operative recovery room and again within the first 24 hours after surgery. Reno grams are then obtained on a daily basis for approximately one week and at van ous times thereafter. Interpretation of the renogram curves is modified after previously reported series ( 2,3 ) . The renogram is thus divided into three segments which relate in pant to the vascular supply, secretory activity, and excretion from the kidney. Our results show that the renogram is a sensitive indicator of the function of the renal transplant. We have observed a variety of patterns which appear to be related to the acceptance or rejection of a transplant. During a rejection phase the “typical―change in the normal pattern is an elevation of the curve of the ex cretory segments and a gradual depression of the “functional―peak. Outflow obstruction and in some cases compromise of the vascular supply may compli cate the interpretation of a rejection pattern. The following is a brief case history of one of our patients (T. B. ), age 15, who was considered as a candidate for transplantation because of renal failure secondary to chronic glomerulonephritis. On September 28, 1963, she received two cadaver kidneys. Figure 1 shows a typical normal nenognam pattern together with selected nenograms on these transplanted kidneys. Figure 2 shows results of some of the laboratory tests. The nenognam performed on September 30, indicates a gradual increase in the concentration of the isotope in both transplanted kid neys. There is no evidence of an excretory component, although moderate urine 1Creatinine clearances are all normalized to 1.73 M' body area. Pottern of Normol Hippuron Renogrom 0-8-63 @64 ‘225 63 4•22-64 @ç4@@2\J4__5@2S44 Fig. 1. Upper left demonstrates a normal renogram. Rejection reactions were clinically and chemically present on 10/8/63, 12/25/63 and 4/11/64. RADIOISOTOPE RENOCEAM IN KIDNEY TRANSPLANTS 809 output was measured. The pattern resembles somewhat that seen in early rejec lion but was thought here to represent tubular damage secondary to the ischemia of the kidneys prior to completion of the transplantation. The BUN was 36 mg % and the cneatinine clearance was 60 liters/24 hours at this time.1 The renogram on October 8 resembles closely a nephrectomy pattern bilaterally, and at this time there was scanty urine output. The BUN had risen to 101 mg %and the cre atinine clearance had dropped to less than 10 liters/24 hours. By October 16 the patient's urine output had increased to 1,500 cc per day, the BUN had dropped to 44 mg % and the creatinine clearance had risen to 35 liters/24 hours. At this time an improvement of the renognam may be noted, especially on the right kid ney, which appears to show, in addition to some function, a slight excretory com ponent. On October 25 good function is seen bilaterally and good excretion is seen on the renogram of the right kidney. There is some delay of excretion from the left kidney. Two weeks later, on November 6, the nenograms have approached normal pattern bilaterally and the patient's clinical status was vastly improved over that of previous weeks. The BUN had fallen to 28 mg % with little change in the creatinine clearance. The patient was discharged about this time. During the next several weeks there was gradual improvement of the reno gram pattern. The BUN dropped to a low of 16 mg %and the creatinine clearance rose to a high of 90 liters/24 hours. There was no change in medications during this time, with the patient on a maintenance dose of Imuran. Beginning about December 6, there was a gradual rise in the BUN and drop in creatinine clear ance. The patient was re-admitted to the hospital on December 24 with acute renal failure. The renognam pattern at this time again resembled closely a “neph rectomy pattern.― The BUN had risen to 54 mg %,the serum creatinine was 3.8 mg %and the creatinineclearancehad droppedbelow 5 liters/24 hours.The urine I @@@‘°: H- @ftINflN Ih o lb __________________IlIIIIOhIIIIIIllhIIIi@lMUMII@ .@ I I, 8 1 I I Fig. 2. Chronological presentation of chemical determinations and immunosuppressive drug therapy. Rejection reactions were felt to be present on 10/8/63, 12/25/63 and 4/11/64. 810 LOKEN,STAAB,VERNIERANDKELLY output had been decreasing steadily prior to this admission. Intensive drug ther apy was instituted and rapid improvement of the patient's renal status was ob served. The renogram pattern obtained on January 13, 1964 reflects this improve ment as did, a BUN of 40 mg %and a creatinine clearance of 114 liters/24 hours. It may also be noted that the renal function appears to be slightly better in the right kidney. Continued improvement of this patient's clinical status was observed dur ing the ensuing weeks. The pattern of the nenogram likewise improved as may be evidenced by that obtained on January 29. Since that time, there have been two more episodes of rejection reaction noted, both of which were less severe than that observed in December, 1963. At present, this patient continues to do well. SUMMARY Abnormal patterns have been obtained at various times following the trans plants. Delayed excretory phase with a gradual depression of the functional peak has been the most consistent pattern seen during a rejection reaction. Our inter pretation of the renognam pattern does not always correlate with the clinical status. In some cases an abnormal pattern persists despite an improvement in urine output and blood chemistries. Continued investigation in man and ani mals as to the value of the renogram in kidney transplants is being carried out. REFERENCES 1. COLLINS, J. J., JR., PLZAK, L. F., TAMVAKOPOULOS, S. K. AND WILSON, R. E. : Serial Reno grams after Kidney Transplantation in Man. Surg. Forum 14:217, 1963. 2. TAUXE, W. N., HUNT, J. C. AND BURBANK, M. K. : Radioisotope Renogram ( Orthoiodohip purate-I'°') : Standardization of Technique and Expression of Data. Amer. I. Clin. Path., 37:567, 1962. 3. WINTER, CHESTER C.: Radioisotope Renography: A Kidney Function Test Performed with Radioisotope-Labeled Agents. The Williams and Wilkins Company, Baltimore, 1963..